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目的建立一种快速、灵敏的测定人血浆中氯沙坦/氢氯噻嗪(抗高血压药)浓度的高效液相色谱串联质谱法,并评价2种氯沙坦钾氢氯噻嗪片在健康志愿者体内的生物等效性。方法20例健康男性志愿者,用随机双交叉试验方法,单剂量口服受试或参比氯沙坦钾氢氯噻嗪片(50mg/12.5mg),用HPLC-MS/MS法测定血浆中氯沙坦/氢氯噻嗪浓度。结果20名健康男性受试者口服含氯沙坦钾50mg、氢氯噻嗪12.5mg的受试制剂和参比制剂后,氯沙坦:tmax分别为(1.09±0.56)、(1.12±0.55)h,Cmax分别为(118.9±68.9)、(110.2±51.0)ng·mL-1,t1/2分别为(3.15±0.76)、(2.96±0.71)h,AUC0-t分别为(226.2±65.0)、(241.9±77.4)ng.h.mL-1,AUC0-∞分别为(250.5±68.7)、(265.7±81.5)ng.h.mL-1;氢氯噻嗪:tmax分别为(1.93±0.54)、(2.25±0.60)h,Cmax分别为(73.2±11.0)、(74.5±17.4)ng·mL-1,t1/2分别为(9.45±3.57)、(8.33±2.58)h,AUC0-t分别为(401.8±138.3)、(390.6±149.3)ng.h.mL-1,AUC0-∞分别为(438.2±146.8)、(415.5±156.1)ng.h.mL-1。以氯沙坦AUC0-t计算,氯沙坦钾氢氯噻嗪片中氯沙坦与氢氯噻嗪相对生物利用度分别平均为(96.5±21.2)、(106.8±22.9)%。结论受试制剂与参比制剂在人体内具有生物等效性。
Objective To establish a rapid and sensitive method for the determination of losartan / hydrochlorothiazide (antihypertensive) in human plasma by high performance liquid chromatography-tandem mass spectrometry and to evaluate the bioavailability of 2 losartan potassium hydrochlorothiazide tablets in healthy volunteers Equivalence. Methods Twenty healthy male volunteers were randomized, double-crossover, single-dose orally or losartan potassium hydrochlorothiazide (50 mg / 12.5 mg) to determine the plasma losartan / Hydrochlorothiazide concentration. Results Losartan: tmax was (1.09 ± 0.56) and (1.12 ± 0.55) h, respectively, in 20 healthy male subjects after oral administration of 50 mg losartan and 12.5 mg hydrochlorothiazide. (110 ± 51.0) ng · mL-1 and (3.15 ± 0.76) and (2.96 ± 0.71) h respectively, and the AUC0-t were (226.2 ± 65.0) and ± (250) ± 68.7, (265.7 ± 81.5) ng.h.mL-1, respectively. The values of tmax in hydrochlorothiazide were (1.93 ± 0.54) and (2.25 ± 0.60 ) h and Cmax were (73.2 ± 11.0) and (74.5 ± 17.4) ng · mL-1, respectively. The values of t1 / 2 were 9.45 ± 3.57 and 8.33 ± 2.58 h respectively. The AUC0-t were (401.8 ± 138.3) ), (390.6 ± 149.3) ng.h.mL-1, and AUC0-∞ were (438.2 ± 146.8) and (415.5 ± 156.1) ng.h.mL-1, respectively. The relative bioavailability of losartan and hydrochlorothiazide in losartan potassium hydrochlorothiazide tablets was (96.5 ± 21.2) and (106.8 ± 22.9)%, respectively, on the basis of losartan AUC0-t. Conclusion The test preparations and reference preparations have bioequivalence in human body.